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During the congress, E-Posters will be accessible to all participants on the congress website 24/7, as well as in the E-poster stations in the congress center.
Preparing your E-Poster
Please review the E-Poster format requirements carefully when preparing your E-Poster. Should your E-Poster not meet the mentioned requirements, it may not be displayed as described above.
E-Poster Submission Deadline
Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
Please follow the instructions below to input your abstract title.
Abstract titles should be brief and reflect the content of the abstract.
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide, and podocyte loss plays a central role in driving DKD progression. However, the mechanisms underlying podocyte repair and regeneration in DKD remain poorly understood. In this study, we investigated podocyte heterogeneity and regenerative mechanisms in DKD.
Single-cell RNA sequencing (scRNA-seq) was performed on 109,147 cells from diabetic mouse kidneys. Combined with human spatial transcriptomics and multicolor immunofluorescence, we defined the functional characteristics and spatial localization of distinct podocyte subpopulations. Pseudotime trajectory and ligand–receptor interaction analyses were used to characterize changes in PEC–podocyte communication under DKD. A DKD mouse model was treated with the lysine-specific demethylase 1A (KDM1A) inhibitor GSK2879552 (5 mg/g/day by gavage for 8 weeks) and albuminuria as well as mesangial matrix expansion were evaluated. In vitro, primary PECs and podocyte were co-cultured and stimulated with recombinant Jag1 ligand. Moreover, we detected the expression of the Notch2 target gene affected by KDM1A through transcriptome sequencing.
Single-cell RNA sequencing analysis revealed substantial heterogeneity among podocytes in DKD. We identified a previously unrecognized metabolic subpopulation, termed Cryabʰⁱ_podo, which exhibits high oxidative phosphorylation activity and enrichment of mitochondrial proteins, distinguishing it from differentiated mature podocytes. Multicolor immuno- fluorescence confirmed that Cryabʰⁱ_podo colocalize with the mature podocyte marker synaptopodin, but not with the slit diaphragm protein Magi2. Further analysis of clinical samples indicated that the abundance of Cryabʰⁱ_podo is negatively correlated with urinary protein and serum creatinine levels and positively correlated with estimated agglomerate filtration rate (eGFR) in DKD patients. In addition, among parietal epithelial cell (PEC) subpopulations, we also identified a Cdkn1aʰⁱ_ PECs subset enriched in podocyte-associated signatures, located near both the vascular and urinary poles adjacent to podocyte. This suggests that Cdkn1aʰⁱ_PECs may act as progenitor cells capable of partially compensating for podocyte function or transitioning into podocyte. Pseudotime trajectory and interaction analyses further found Jag1-Notch2 signaling as a key mediator of PEC-to-podocyte conversion. Stimulation with Jag1 promoted podocyte redifferentiation, indicating that activation of the Notch2 pathway is a crucial mechanism in this transition. Furthermore, transcriptomic profiling showed that inhibition of lysine demethylase 1A (KDM1A) with GSK 2879552 upregulates histone H3 lysine 4 mono-/di-methylation (H3K4me1/2), leading to reactivation of Notch2 target genes and restoration of podocyte numbers.
Collectively, these findings provide novel mechanistic insights and highlight potential therapeutic targets for podocyte repair and regeneration in DKD.
